Barney S. Graham
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View article: Multivalent Antigen Display on Nanoparticles Diversifies B Cell Responses
Multivalent Antigen Display on Nanoparticles Diversifies B Cell Responses Open
Nanoparticles for multivalent display and delivery of vaccine antigens have emerged as a promising avenue for enhancing B cell responses to protein subunit vaccines. Here, we evaluated B cell responses in rhesus macaques immunized with pre…
View article: Human Coronavirus HKU1 Neutralizing Monoclonal Antibodies Target Diverse Epitopes Within and Around the TMPRSS2 Receptor Binding Site
Human Coronavirus HKU1 Neutralizing Monoclonal Antibodies Target Diverse Epitopes Within and Around the TMPRSS2 Receptor Binding Site Open
Endemic human coronaviruses (HCoVs), like HCoV-HKU1, account for ∼30% of common cold/year and can cause serious upper and lower respiratory infections, yet no licensed vaccines target HCoVs. In fact, little is known about HCoV-HKU1’s antig…
View article: Structural convergence and water-mediated substrate mimicry enable broad neuraminidase inhibition by human antibodies
Structural convergence and water-mediated substrate mimicry enable broad neuraminidase inhibition by human antibodies Open
Influenza has been responsible for multiple global pandemics and seasonal epidemics and claimed millions of lives. The imminent threat of a panzootic outbreak of avian influenza H5N1 virus underscores the urgent need for pandemic preparedn…
View article: Structural serology of polyclonal antibody responses to mRNA-1273 and NVX-CoV2373 COVID-19 vaccines
Structural serology of polyclonal antibody responses to mRNA-1273 and NVX-CoV2373 COVID-19 vaccines Open
Design and development of improved COVID-19 vaccines that can induce broad, durable immunity against emerging variants require an in-depth understanding of the antigenic and immunogenic properties of vaccines utilizing existing platforms. …
View article: Decoding respiratory syncytial virus morphology: distinct structural and molecular signatures of spherical and filamentous particles
Decoding respiratory syncytial virus morphology: distinct structural and molecular signatures of spherical and filamentous particles Open
Respiratory syncytial virus (RSV) is a pleomorphic enveloped virus that buds as both spherical and filamentous particles. The determinants of RSV particle morphology and the roles of these forms in transmission and pathogenicity are not cl…
View article: Evaluation of a nanoparticle influenza vaccine in the pig model
Evaluation of a nanoparticle influenza vaccine in the pig model Open
Influenza A virus (IAV) infection causes substantial disease burden and vaccines capable of conferring broad immunity are lacking, necessitating frequent reformulation of seasonal vaccines. The purpose of this study was to evaluate the imm…
View article: MERS-CoV spike vaccine-induced N-terminal domain-specific antibodies are more protective than receptor binding domain-specific antibodies
MERS-CoV spike vaccine-induced N-terminal domain-specific antibodies are more protective than receptor binding domain-specific antibodies Open
The COVID-19 pandemic underscores the need to prepare for future emerging coronavriuses (CoVs) by understanding the principles behind effective CoV vaccine design such as protective immunity and antibody responses. To study which epitopes …
View article: Structural serology of polyclonal antibody responses to mRNA-1273 and NVX-CoV2373 COVID-19 vaccines
Structural serology of polyclonal antibody responses to mRNA-1273 and NVX-CoV2373 COVID-19 vaccines Open
Summary Current COVID-19 vaccines are largely limited in their ability to induce broad, durable immunity against emerging viral variants. Design and development of improved vaccines utilizing existing platforms requires an in-depth underst…
View article: Structural Convergence and Water-Mediated Substrate Mimicry Enable Broad Neuraminidase Inhibition by Human Antibodies
Structural Convergence and Water-Mediated Substrate Mimicry Enable Broad Neuraminidase Inhibition by Human Antibodies Open
Influenza has been responsible for multiple global pandemics and seasonal epidemics and claimed millions of lives. The imminent threat of a panzootic outbreak of avian influenza H5N1 virus underscores the urgent need for pandemic preparedn…
View article: Modulating the immunodominance hierarchy of immunoglobulin germline-encoded structural motifs targeting the influenza hemagglutinin stem
Modulating the immunodominance hierarchy of immunoglobulin germline-encoded structural motifs targeting the influenza hemagglutinin stem Open
Antibodies targeting epitopes through germline-encoded motifs can be found in different individuals. While these public antibodies are often beneficial, they also pose hurdles for subdominant antibodies to emerge. Here, we use transgenic m…
View article: Structure-based design of glycoprotein subunit vaccines for mumps
Structure-based design of glycoprotein subunit vaccines for mumps Open
Mumps virus (MuV) is a highly contagious paramyxovirus that is endemic in most regions of the world and continues to cause outbreaks even in highly immunized populations. Outbreaks of mumps in countries with high measles, mumps, and rubell…
View article: pr-independent biogenesis of infectious mature Zika virus particles
pr-independent biogenesis of infectious mature Zika virus particles Open
Flavivirus assembly at the endoplasmic reticulum is driven by the structural proteins envelope (E) and premembrane (prM). Here, contrary to the established paradigm for flavivirus assembly, we demonstrate that the biogenesis of flavivirus …
View article: B.2 Time from symptom onset and number of health care encounters prior to diagnosis of cerebral venous thrombosis
B.2 Time from symptom onset and number of health care encounters prior to diagnosis of cerebral venous thrombosis Open
Background: Cerebral venous thrombosis (CVT)most commonly affects younger women. Diagnosis may be delayed due to its distinct presentation and demographic profile compared to other stroke types. Methods: We examined delays to diagnosis of …
View article: Heterologous cAd3-Ebola and MVA-EbolaZ vaccines are safe and immunogenic in US and Uganda phase 1/1b trials
Heterologous cAd3-Ebola and MVA-EbolaZ vaccines are safe and immunogenic in US and Uganda phase 1/1b trials Open
Ebola virus disease (EVD) is a filoviral infection caused by virus species of the Ebolavirus genus including Zaire ebolavirus (EBOV) and Sudan ebolavirus (SUDV). We investigated the safety and immunogenicity of a heterologous prime-boost r…
View article: Protective human monoclonal antibodies target conserved sites of vulnerability on the underside of influenza virus neuraminidase
Protective human monoclonal antibodies target conserved sites of vulnerability on the underside of influenza virus neuraminidase Open
Continuously evolving influenza viruses cause seasonal epidemics and pose global pandemic threats. Although viral neuraminidase (NA) is an effective drug and vaccine target, our understanding of the NA antigenic landscape still remains inc…
View article: Prefusion stabilization of the Hendra and Langya virus F proteins
Prefusion stabilization of the Hendra and Langya virus F proteins Open
Pathogenic henipaviruses such as Nipah virus (NiV) and Hendra virus (HeV) cause respiratory symptoms, with severe cases resulting in encephalitis, seizures, and coma. The work described here shows that the NiV and HeV fusion (F) proteins s…
View article: Vaccination with prefusion-stabilized respiratory syncytial virus fusion protein elicits antibodies targeting a membrane-proximal epitope
Vaccination with prefusion-stabilized respiratory syncytial virus fusion protein elicits antibodies targeting a membrane-proximal epitope Open
Respiratory syncytial virus (RSV) causes tens of millions of acute lower respiratory tract infections and millions of hospital admissions globally each year. An antibody repertoire analysis of a human vaccine trial investigating a prefusio…
View article: Multivalent antigen display on nanoparticle immunogens increases B cell clonotype diversity and neutralization breadth to pneumoviruses
Multivalent antigen display on nanoparticle immunogens increases B cell clonotype diversity and neutralization breadth to pneumoviruses Open
Nanoparticles for multivalent display and delivery of vaccine antigens have emerged as a promising avenue for enhancing B cell responses to protein subunit vaccines. Here, we evaluated B cell responses in rhesus macaques immunized with pre…
View article: Refined semi-lethal aerosol H5N1 influenza model in cynomolgus macaques for evaluation of medical countermeasures
Refined semi-lethal aerosol H5N1 influenza model in cynomolgus macaques for evaluation of medical countermeasures Open
Highly pathogenic avian influenza A H5N1 viruses cause high mortality in humans and have pandemic potential. Effective vaccines and treatments against this threat are urgently needed. Here, we have refined our previously established model …
View article: Self-assembling SARS-CoV-2 spike-HBsAg nanoparticles elicit potent and durable neutralizing antibody responses via genetic delivery
Self-assembling SARS-CoV-2 spike-HBsAg nanoparticles elicit potent and durable neutralizing antibody responses via genetic delivery Open
While several COVID-19 vaccines have been in use, more effective and durable vaccines are needed to combat the ongoing COVID-19 pandemic. Here, we report highly immunogenic self-assembling SARS-CoV-2 spike-HBsAg nanoparticles displaying a …
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View article: Antigen spacing on protein nanoparticles influences antibody responses to vaccination
Antigen spacing on protein nanoparticles influences antibody responses to vaccination Open
SUMMARY Immunogen design approaches aim to control the specificity and quality of antibody responses to enable the creation of next-generation vaccines with improved potency and breadth. However, our understanding of the relationship betwe…
View article: EV-D68 virus-like particle vaccines elicit cross-clade neutralizing antibodies that inhibit infection and block dissemination
EV-D68 virus-like particle vaccines elicit cross-clade neutralizing antibodies that inhibit infection and block dissemination Open
Enterovirus D68 (EV-D68) causes severe respiratory illness in children and can result in a debilitating paralytic disease known as acute flaccid myelitis. No treatment or vaccine for EV-D68 infection is available. Here, we demonstrate that…
View article: Genetic immunization with self-assembling SARS-CoV-2 Spike-HBsAg nanoparticles
Genetic immunization with self-assembling SARS-CoV-2 Spike-HBsAg nanoparticles Open
As the COVID-19 pandemic continues to pose a great challenge to global health, more effective and durable vaccines are needed owing to the waning protection offered by the current available vaccines. Here we report highly immunogenic self-…